title: Measles virus nonstructural C protein modulates viral RNA polymerase activity by interacting with host protein SHCBP1.
abstract: Most viruses possess strategies to circumvent host immune responses. The measles virus (MV) nonstructural C protein suppresses the interferon response, thereby allowing efficient viral growth, but its detailed mechanism has been unknown. We identified Shc Src homology 2 domain-binding protein 1 (SHCBP1) as one of the host proteins interacting with the C protein. Knockdown of SHCBP1 using a short-hairpin RNA greatly reduced MV growth. SHCBP1 was found to be required for viral RNA synthesis in the minigenome assay and to bind to the MV phosphoprotein, a subunit of the viral RNA polymerase. A stretch of 12 amino acid residues in the C protein were sufficient for SHCBP1 binding, and the peptide containing these 12 residues could suppress MV RNA synthesis, like the full-length C protein. The central region of SHCBP1 was found to bind to the C protein, as well as the phosphoprotein, but the two viral proteins did not compete for SHCBP1 binding. Our results indicate that the C protein modulates MV RNA polymerase activity by binding to the host protein SHCBP1. SHCBP1 may be exploited as a target of antiviral compounds.
authors.affiliation: Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Ito
authors.forename: Masaharu
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
authors.forename: Takanori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yanagi
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohno
mesh_terms: D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000502:physiology*; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D008954:Models, Biological; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D055765:Shc Signaling Adaptor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C584392:C protein, measles virus; D012367:RNA, Viral; D055765:Shc Signaling Adaptor Proteins; C118247:Shcbp1 protein, mouse; D017361:Viral Nonstructural Proteins; D012321:DNA-Directed RNA Polymerases